Figure 1.
Image of a hydrogel reservoir with one end closed by a silicone septum for fluid injections (right end), while the other end is open in order to release the drug into the area to be addressed (left end) and calculation of the amount of drug inside the hydrogel filled tube.
Drug release from this arrangement is shown in the diagram. The data points result from nine experiments from three different NCO-sP(EO-stat-PO) batches, each of them used for the preparation of three release setups.
Figure 2.
Cross-section images of silicone tubes before and after filling between 2 and 10 mm with with 20 mm with with 20% (w/v) NCO-sP(EO-stat-PO) gels (top left and middle), after drying of the gel (top right), re-swelling (bottom right) and after maintaining the gels in a swollen condition for 50 days (bottom left).
Figure 3.
Mean and SEM of hearing loss (difference between the experimental days hearing threshold and hearing threshold before implantation) development from day 3 to day 28 for all experimental groups.
Cochleae of the trauma group (n = 12) suffered from highest hearing loss compared to all other experimental groups. Additionally, individuals implanted with a PBS releasing reservoir (n = 12) lost hearing more significantly compared to the group having been implanted with the DEX filled reservoir (n = 14). The statistical differences using ANOVA test examined on experimental day 28 are plotted at the right side of the graph, demonstrating, that the reservoir + DEX treatment resulted in the significantly best hearing thresholds. (** = p<0.01; *** = p<0.001).
Figure 4.
Graphed t-test results of tissue growth ranking (A) and measurement (B) for the whole cochlea length.
Using both evaluation methods the tissue growth in the trauma group was significantly increased compared to the reservoir and DEX group with a p value <0.001. When applying the ranking score the difference between reservoir + PBS and trauma or reservoir + DEX was significant with p<0.05 (A). Comparing the tissue growth of the reservoir + PBS group with those of the trauma group or the DEX group using the measuring method, the p value is <0.001 (PBS vs. trauma) and <0.05 (PBS vs. DEX). Error bars: SEM. * = p<0.05, *** = p<0.001.
Figure 5.
Distribution of fibrosis regarding subjective ranking for all inner ear turns and all experimental groups.
In all groups the highest extend of connective tissue growth was detected in the basal turns. Fibroblast growth in more apical turns was only detected in the trauma group and did not take place in reservoir groups at all. Significant differences between the groups were detected (plotted above the SEM bars: * = p<0.05, *** = p<0.001; reference of the significance is marked by the thick bar) and were most prominent in the lower basal turns (p<0.001). Even though there seems to be a tendency of increased tissue formation in the PBS group compared to the DEX group there is no statistical relevance detectable using One-way ANOVA in combination with the Tukey post-test to compare the means between groups.
Figure 6.
In this graph the mean and SEM percentage of measurement of connective tissue growth in the scala tympani of all experimental groups for each cochlear turn from basal to apical are plotted.
The comparison of tissue growth between the groups is illustrated by horizontal lines. Reference of the significance is marked by the thick bar. Highly significant differences were observed between tissue growth in the trauma group and groups receiving PBS or DEX by reservoir. No differences were measured between PBS or DEX treated groups even though a slightly increased connective tissue growth seems to be apparent in the PBS group compared to DEX treated animals. In cochleae implanted with a PBS releasing reservoir tissue growth could be measured from basal up to the 2nd middle turn whereas in the reservoir and DEX treated cochleae connective tissue formation was only visible in the lower and upper basal region. One-way ANOVA in combination with the Tukey post-test was used to compare means between groups: * = p<0.05; ** = p<0.01; *** = p<0.001.
Figure 7.
Correlation of hearing loss measured on day 28 and tissue reaction determined by ranking.
Graph A illustrates that with the amount of tissue reaction evaluated over the whole cochlea length the loss of residual hearing in all frequencies increases (p<0.001; r = 0.6338). This effect is detectable in lower and higher frequency regions of the cochleae as well. In figure 7B the detected tissue reaction and hearing loss at the upper basal turn and at 32 kHz are plotted as an example for the correlation in higher frequency areas 7B the detected tissue reaction and hearing loss at the upper basal turn and at 32 kHz are plotted as an example for the correlation in higher frequency areas kHz are plotted as an example for the correlation in higher frequency areas (p<0.05; r = 0.3742). Fig. C is an example for correlation of tissue reaction and hearing loss in lower frequency areas of the cochlea. Here we correlated hearing loss at 1 kHz and tissue growth in the 3 kHz and tissue growth in the 3rd middle turn (p<0.05; r = 0.3727).